Postoperative pharmacotherapy for patients with biliary atresia in Japan.

BACKGROUND: Members of the Japanese Biliary Atresia Society were surveyed using questionnaires that assess their current practice regarding postoperative pharmacotherapy for outpatients with biliary atresia (BA). METHODS: In September 2018, questionnaires were sent to 100 member institutions of the Japanese Biliary Atresia Society. Questionnaires included the number of BA outpatients per institution and pharmacotherapy for outpatients with native liver. Pharmacotherapies were categorized into antibiotics, cholagogues, hepatoprotective agents, branched-chain amino acid supplement, Japanese Kampo medicine, probiotics, laxative, glycerin enema, and "others." In each category, the questionnaires asked about the medicine's details and the time of withdrawal of administration. RESULTS: Responses were collected from 58 of the 100 institutions. Fifty-four institutions (94.7%) had prescribed one or more medicines as postoperative pharmacotherapy, and three institutions (5.3%) did not prescribe any medicines. Fifty-three institutions (93.0%) had prescribed ursodeoxycholic acid (UDCA), and 32 (60.4%) of these continued prescribing UDCA as long as the condition of patients remained unchanged. Twenty-nine (50.9%) had prescribed Japanese Kampo medicines ("Inchinkoto" in all cases). Twenty-four (42.1%) had prescribed antibiotics, mainly trimethoprim-sulfamethoxazole, in 21 (87.5%). Twenty-three (40.4%) had prescribed probiotics. CONCLUSIONS: There were many variations of pharmacotherapy in BA outpatients with native liver in Japan, including antibiotic, probiotic, and Inchinkoto prescriptions. Of the various drugs, the most commonly administered was UDCA.

Quality of life of caregivers supporting neurologically impaired patients who underwent surgery.

BACKGROUND: A questionnaire survey was conducted to clarify whether surgical treatments performed by a pediatric surgeon improve the quality of life (QOL) of caregivers (medical doctors, nurses, physical therapists, and nursery teachers) supporting neurologically impaired (NI) patients who work at specialized institutions. METHODS: The questionnaire survey was conducted with caregivers who cared for NI patients who underwent an operation at the Department of Pediatric Surgery, Kurume University Hospital. Quality-of-life related responses concerning the change of care after surgical procedures in NI patients were collected in addition to the background data related to caregivers and the surgical procedures performed for them. Degrees of difficulty in caring for NI patients and of the caregivers' own QOL postoperatively were also compared. RESULTS: There were 192 valid responses. The majority of responses were from females and nurses aged in their 40s and 50s. The surgical procedure performed most often in the NI patients was gastrostomy. Of the respondents, 77% answered that the postoperative care became easier. The degrees of difficulty in caring for NI patients and the caregivers' own QOL were significantly higher and lower, respectively, among physical therapists compared with caregivers in other occupations. Moreover, the QOL in respondents with factors related to a longstanding relationship with NI patients was significantly higher compared with the respondents without them. CONCLUSION: This survey indicated that surgical procedures for NI patients might contribute to improved QOL for the caregiver by reducing the difficulty of caring for NI patients.

Current status of intractable pediatric gastroesophageal reflux disease in Japan: a nationwide survey.

PURPOSE: A nationwide survey was conducted to investigate the current status of pediatric gastroesophageal reflux disease (GERD) in Japan, with special reference to the characteristics of intractable GERD. METHODS: Data were collected using a questionnaire from facilities specializing in the treatment of pediatric GERD in Japan. Intractable GERD was defined as follows: I, no symptomatic improvement after 8 weeks of optimal medical treatment (OMT) plus fundoplication; II, no symptomatic improvement after 8 weeks of OMT and with no indications for fundoplication; and III, no symptomatic improvement after surgery without OMT. RESULTS: We collected data from 3,463 pediatric patients with GERD from 91 institutions, and 81 satisfied the definition of intractable GERD. Additional clinical information was obtained from 56 patients, and 41 represented cases of definite intractable GERD. The main underlying disorders included neurological impairment (NI), esophageal atresia (EA), and congenital heart disease (CHD), which altogether accounted for 85% of patients. Of the 41 patients, 33 received fundoplication, and the remaining 8 received medical treatment alone because surgery was considered unsuitable. CONCLUSIONS: The nationwide survey revealed that pediatric intractable GERD is rare in Japan. Three main underlying disorders-NI, EA, and CHD-were implicated in the majority of cases of intractable GERD.

Complications in patients with neurological impairment after gastrostomy.

BACKGROUND: Neurological impairment (NI) is responsible for most conditions that require a permanent gastrostomy tube. The present study assessed the occurrence of short- and long-term complications after video-assisted gastrostomy (VAG) in patients with NI. METHODS: The incidence of short- (<6 months) and long-term (over 2 years) complications of VAG were analyzed in a retrospective study. The differences between the incidence of the complications of VAG according to the age at surgery (≤15 years vs. ≥16 years) were also evaluated. The short- and long-term complications observed were granulation tissue formation, infection requiring antibiotic treatment, skin problems, perigastrostomy leakage, vomiting, accidental tube dislodgement, dumping syndrome, ileus, and peritonitis. RESULTS: Eighty-two patients were evaluated for short- and long-term complications. The long-term complication rate was significantly lower than the short-term complication rate (P = 0.0026). Onodera's prognostic nutritional index before VAG in patients with long-term complications was significantly lower than in patients without such complications (P = 0.046). The incidence of long-term granulation tissue formation, infection, and vomiting were significantly lower than those of similar short-term complications. Long-term skin problems were associated with short-term skin problems (odds ratio: 18.95; 95% confidence interval: 4.53-92.98; P < 0.001). The number of patients ≥16 years old with short- and long-term skin problems was significantly higher than in patients ≤15 years old (P = 0.0014 and P = 0.0073, respectively). CONCLUSIONS: The incidence rate of granulation tissue formation and infection after VAG were lower in the long term than in the short term. However, patients ≥16 years old presented with persistent complications.

The herbal medicines Inchinkoto and Saireito improved hepatic fibrosis via aquaporin 9 in the liver of a rat bile duct ligation model.

OBJECTIVE: To determine if the administration of the Japanese herbal medicines Inchinkoto (ICKT) and Saireito (SRT) ameliorate hepatic fibrosis and derangement of hepatocyte aquaporins (AQPs) following bile duct ligation (BDL) in a rat model of obstructive cholestasis. MATERIALS AND METHODS: Five groups of Wistar rats were used, and the groups included sham surgery (Sham group), BDL with no treatment (NT group), BDL plus ICKT (ICKT group), BDL plus SRT (SRT group), and BDL plus ICKT and SRT (SRT/ICKT group). Each herbal medicine was administered at 1 g/kg/day on the first postoperative day. The serum levels and various clinical markers were measured with real-time polymerase chain reaction. Staining was used to evaluate the degree of fibrosis and the inflammatory responses. RESULTS: Serum aspartate aminotransferase and alanine aminotransferase in the ICKT and SRT/ICKT groups were significantly lower than those in the NT group. NF-κB mRNA expression was significantly decreased in the ICKT group and the SRT/ICKT group compared with the NT group. AQP9 mRNA expression was significantly increased in the ICKT group and the SRT/ICKT group compared with the NT group. The degree of Masson's trichrome staining in the SRT/ICKT group was significantly lower than that in the NT group. The degree of NF-κB staining in the SRT/ICKT group was significantly lower than that in the NT, ICKT, or SRT group. CONCLUSIONS: The postoperative administration of ICKT and SRT induced synergistic beneficial effects, resulting in the reduction of hepatic fibrosis via mechanisms involving the inhibition of NF-κB expression and the improvement of AQP9 downregulation.

The management and outcome of pediatric blunt chest-abdominal injuries.

BACKGROUND: The aim of this study was to determine the frequency and nature of pediatric blunt chest-abdominal injuries (BCAIs) and to summarize their management, ranging from non-operative management (NOM), with or without angioembolization (AE), to surgical treatment. METHODS: This retrospective study included patients admitted to our hospital for BCAIs from January 1996 to December 2017. The age, injury pattern, organs of injury, outcome, and treatment were summarized. RESULTS: One hundred and thirty-two patients (98 males, 34 females, mean age 7.68 years ± 3.58, range 1-15 years) were included in the study. Their injuries resulted from motor-vehicle traffic incidents (n = 60), single-bicycle injuries (n = 16), falls (n = 33), sports (n = 10), assault (n = 6), abuse (n = 3), and others (n = 4). There were no injured organs in 31 cases, while there were 130 injured organs in 101 cases, including the liver (n = 42), spleen (n = 35), lung (n = 23), kidney (n = 13), intestine (n = 10), pancreas (n = 5), and adrenal gland (n = 2). Angiography (AG) was performed in 20 cases, and NOM with AE was performed in 16 cases, including 17 organs (liver injury [n = 9], splenic injury [n = 5], and kidney injury [n = 4]). Surgical treatment was performed in eight cases (splenic injury in one, pancreas injury in one, and intestinal injury in six). NOM without AE was performed in the other cases. CONCLUSIONS: The management of organ injury must take into consideration the management of integrated bleeding. It is recommended that children with severe organ injury are treated in dedicated trauma centers in which AE is available.

Standard protocol devised by the Japanese Pediatric Impedance Working Group for combined multichannel intraluminal impedance-pH measurements in children.

Multichannel intraluminal impedance-pH measurements (MII-pH) are useful for evaluating acid and non-acid gastroesophageal reflux (GER). However, the use of MIH-pH is not yet established in Japan. The Japanese Pediatric Impedance Working Group (Japanese-PIG) convened to devise a standard protocol for MII-pH in Japanese children. The expert members of the Japanese-PIG collected data on pediatric MII-pH from the relevant literature in English, including the standard protocol of MII-pH presented by the European PIG, and the insights of international experts. The resultant consensus was included in the contents of the standard protocol of MII-pH. The standard protocol included standardization of the indication, methodology, and interpretation of MII-pH in Japanese children. The criteria for abnormal GER by MII-pH were defined using the Reflux Index and number of total reflux episodes independently in children aged < 1 year and those aged ≥ 1 year. Moreover, a significant relationship between GER and symptoms was identified using the symptom index and symptom association probability approach. We conclude that the current version of the protocol for MII-pH is tentative because it is not based on data from Japanese children. Further studies are needed to render this protocol clinically beneficial and expand its use in Japan.

Correction to: Standard protocol devised by the Japanese Pediatric Impedance Working Group for combined multichannel intraluminal impedance-pH measurements in children.

The authors would like to add the following sentence in Acknowledgements in the original publication of this paper.

The assessment of the esophageal motility of children with esophageal disorders by the detailed observation of the pH-multichannel intraluminal impedance waveform and baseline impedance: screening test potential.

BACKGROUND: The present study aimed to evaluate whether the detailed observation of pH/MII waveforms and the analysis of baseline impedance (BI) values could detect esophageal dysmotility in pediatric patients with esophageal disorders. PATIENTS AND METHODS: Eleven patients with congenital esophageal disorder in whom pH/MII was conducted from April 2011 to June 2015, were enrolled in this study. The diagnoses of the patients were as follows: postoperative esophageal atresia (EA), n = 6; esophageal achalasia (EAch), n = 4; and congenital esophageal stenosis (CES), n = 1. The characteristics of the pH/MII waveform, pathological GERD, BI value, and the average BI value of the 2 distal channels (distal BI; DBI) were analyzed in each disorder. RESULTS: Two EA (33%) patients and one EAch (25%) patient were diagnosed with GERD. The mean DBI values of the EA, EAch and CES patients was 912 ± 550, 2153 ± 915 and 1392 Ω, respectively. The EA patients showed consistently low DBI values. One CES patient and two infantile EAch patients showed postprandial prolonged low DBI values. Whereas, the pH/MII waveforms of the adolescent EAch patients were difficult to interpret due to their extremely low BI values. CONCLUSIONS: The present study demonstrated that the detailed observation of the pH/MII waveforms in all channels and the analysis of BI were useful for evaluating esophageal motility in children with congenital esophageal disorders. In particular, infantile patients with EAch showed DBI findings that were distinct from those of adult EAch patients. Considering the difficulty of performing esophageal manometry in young children, the detailed observation of the pH/MII waveform may help in the diagnosis of esophageal dysmotility in children.

Analyses of the relationship between a 'number of reflux episodes' exceeding 70 and the pH index in neurologically impaired children by evaluating esophageal combined pH-multichannel intraluminal impedance measurements.

BACKGROUND: The present study aimed to evaluate the characteristics associated with a number of reflux episodes (NoRE) of 70 by comparing the clinical and multichannel intraluminal impedance pH measurements (pH/MII) and pH index (pHI) in neurologically impaired (NI) children. PATIENTS AND METHODS: NI children (1-16 years of age) in whom pH/MII had been measured for GERD study were enrolled in this study. All children were divided into NoRE >70 or ≤70 and pHI >4.0 or ≤4.0, >5.0 or ≤5.0 or >7.0 or ≤7.0. In addition, the NI children with pHI >4.0, >5.0 and >7.0 were subdivided into NoRE >70 and ≤70 groups. The clinical and pH/MII measurements were compared between each of the two groups. The cutoff values of pHI and baseline impedance (BI) (Z6) were calculated to discriminate NoRE >70 and ≤70. RESULTS: A total of 61 NI children were enrolled in this study. There was a significant difference in the acid-related parameters, the NoRE (nonacid) and BI between NoRE >70 and ≤70, acid-related parameters and BI between pHI >4.0 and ≤4.0, >5.0 and ≤5.0 and >7.0 and ≤7.0 groups. Furthermore, a significant difference was still observed in the BI between NoRE >70 and ≤70 groups among patients with pHI >4.0, >5.0 or >7.0. The cutoff values of pHI and BI (Z6) for discriminating NoRE >70 and ≤70 were 9.2 and 1049Ω, respectively. CONCLUSION: The present study indicates that NoRE 70 corresponds to GERD in which patients suffer severe acid exposure with pH of around 9% and esophageal mucosal damage with low BI value in NI children.

Pharmacotherapy for pediatric chronic intestinal pseudo-obstruction: Nationwide survey in Japan.

BACKGROUND: Chronic intestinal pseudo-obstruction (CIPO) is a rare disabling and life-threatening disorder characterized by severe impairment of gastrointestinal peristalsis. While a number of pharmacotherapeutics have been developed, only a few trials have been carried out for improvement of the pathological condition of CIPO patients. This report describes the results of a nationwide survey on the pharmacotherapy used in pediatric CIPO in Japan. METHODS: In 2012, a nationwide survey was conducted to identify the clinical presentation of CIPO in Japan. Information was gathered on pharmacotherapy. Four categories were created for medicines used in pharmacotherapy: "probiotics", "Japanese herbal medicines (Kampo medicines)", "laxatives", and "prokinetics". RESULTS: Ninety-two responses were collected from 47 facilities. Of the 62 patients who met the diagnostic criteria, 52 were treated with medications, while the remaining 10 were not. Thirty-four patients were given a total of 49 probiotics; 39 were treated with a total of 50 Kampo medicines; 20 were treated with a total of 28 laxatives; and 26 were given a total of 30 prokinetics, 70% of whom were treated specifically with mosapride. CONCLUSION: Traditional Japanese medicines such as Kampo medicines and mosapride are often used to treat CIPO in Japan. Two combinations, that is, probiotics and Kampo medicines; and Kampo medicines and prokinetics, were often used for pediatric CIPO in Japan.

Internal anal sphincter achalasia: data from a nationwide survey of allied disorders of Hirschsprung's disease in Japan.

PURPOSE: To investigate the incidence and treatment of internal anal sphincter achalasia (IASA) in Japan based on an analysis of data from a nationwide retrospective cohort study of the allied disorders of Hirschsprung's disease. METHODS: Five cases of definitive IASA were collected from a nationwide retrospective cohort study conducted from 2001 to 2010 and a search of the Japanese literature. RESULTS: Symptoms developed during the neonatal period in two patients, during early childhood in two, and at school age in one. Symptoms included abdominal distension with severe constipation (n = 4) and enterocolitis (n = 1). Rectocolonography showed megarectum and no narrow segment in most of the patients. All patients were negative for rectosphincteric reflex. The presence of ganglion cells was demonstrated by H&E or AChE staining from rectal mucosal biopsies or resected full-thickness segments. Two patients were treated conservatively, and three were treated surgically by internal anal sphincter myotomy (n = 2) or Lynn procedure (n = 1), with satisfactory outcomes. CONCLUSION: IASA is a rare but distinct entity in Japan. Although the clinical features of IASA resemble those of short- and ultrashort-segment HD, characteristic pathological findings include the presence of ganglion cells. The outcomes of both conservative and surgical treatment are good.

Clinical Efficacy of Herbal Medicine for Pediatric Lymphatic Malformations: A Pilot Study.

BACKGROUND: Lymphatic malformations (LMs) are congenital malformations of the lymphatic system that commonly affect the head and neck region and cause marked cosmetic and functional complications. In this pilot study, we present eight children with LMs treated using an herbal medicine for this indication. METHODS: Between January 2009 and May 2014, eight children (four boys, four girls) with LMs were treated using oral administration of an herbal medicine, Eppikajyutsuto (TJ-28; Tsumura, Tokyo, Japan), as monotherapy. RESULTS: Four of the cases were macrocystic and four were mixed micro- and macrocystic. The mean treatment duration was 7.2 ± 2.9 months (range 5-12 mos). The mean LM volume shrinkage on magnetic resonance imaging was 54.5 ± 38.3% (macrocystic 73.6 ± 27.0%; mixed micro- and macrocystic 35.4 ± 41.5%). One of four macrocystic lesions had a marked reduction, two had a moderate reduction, and one had no response. A marked reduction was observed in three of the four mixed micro- and macrocystic cases; the other mixed cystic case had no response. The treatment was well tolerated, without severe adverse events. CONCLUSIONS: This preliminary study demonstrates the beneficial effects of TJ-28. Further evaluations of this therapeutic modality are warranted.

Near-infrared fluorescence cholangiography with indocyanine green for biliary atresia. Real-time imaging during the Kasai procedure: a pilot study.

INTRODUCTION: Hepatoportoenterostomy (HPE) with the Kasai procedure is the treatment of choice for biliary atresia (BA) as the initial surgery. However, the appropriate level of dissection level of the fibrous cone (FC) of the porta hepatis (PH) is frequently unclear, and the procedure sometimes results in unsuccessful outcomes. Recently, indocyanine green near-infrared fluorescence imaging (ICG-FCG) has been developed as a form of real-time cholangiography. METHODS: We applied this technique in five patients with BA to visualize the biliary flow at the PH intraoperatively. ICG was injected intravenously the day before surgery as the liver function test, and the liver was observed with a near-infrared camera system during the operation while the patient's feces was also observed. RESULTS: In all patients, the whole liver fluoresced diffusely with ICG-containing stagnant bile, whereas no extrahepatic structures fluoresced. The findings of the ICG fluorescence pattern of the PH after dissection of the FC were classified into three types: spotty fluorescence, one patient; diffuse weak fluorescence, three patients; and diffuse strong fluorescence, one patient. In all five patients, the feces evacuated after HPE showed distinct fluorescent spots, although that obtained before surgery showed no fluorescence. One patient with diffuse strong fluorescence who did not achieve JF underwent living related liver transplantation six months after the initial HPE procedure. Four patients, including three cases involving diffuse weak fluorescence and one case involving spotty fluorescence showed weak fluorescence compared to that of the surrounding liver surface. CONCLUSION: We were able to detect the presence of bile excretion at the time of HPE intraoperatively and successfully evaluated the extent of bile excretion using this new technique. Furthermore, the ICG-FCG findings may provide information leading to a new classification and potentially function as an indicator predicting the clinical outcomes after HPE.

The Evaluation of Gastric Emptying Using the 13 C-Acetate Breath Test in Neurologically Impaired Patients - A Focus on the Stomach Function and Morphology.

PURPOSE: We explored factors affecting gastric emptying in neurologically impaired (NI) patients using the 13C-acetate breath test. METHODS: Twenty-four NI patients were classified by the presence of gastroesophageal reflux disease (GERD), which was treated by fundoplication plus gastrostomy, or the absence of GERD, which was treated by gastrostomy alone, along with gastric malposition involving cascade stomach and organoaxial gastric volvulus (OGV). Gastric emptying parameters (GEPs), which were the emptying half time (T 1/2 , minute), the lag phase time (T lag , minute), and the gastric emptying coefficient (GEC), were measured before and after surgery. We evaluated the relationship between GEPs and GERD, gastric malposition, and surgical intervention. All data were expressed as the median (interquartile range). RESULTS: The T1/2 and GEC of patients with OGV were significantly worse than in those without OGV before surgery (T1/2 with OGV: 241.3 [154.9, 314.3] vs. T1/2 without OGV: 113.7 [105.2, 151.4], p = 0.01, GEC with OGV: 3.19 [2.46, 3.28] vs. GEC without OGV: 3.65 [3.24, 3.90], p = 0.02). GERD and cascade stomach were not associ ated with GEPs. The GEPs of all NI patients showed no significant difference between before and after surgery. The surgical change in T1/2 (ΔT 1/2 ) in the patients with OGV was significantly lower than in those without OGV (ΔT1/2 with OGV: -47.1 [-142.7, -22.1] vs. ΔT1/2 without OGV: -3.78 [-26.6, 12.0], p = 0.03). CONCLUSION: Stomach malposition, such as OGV, seems to affect gastric emptying and may be improved by surgi cal intervention.

Pre and post-operative evaluation of gastroesophageal reflux and esophageal motility in neurologically impaired children using combined pH-multichannel intraluminal impedance measurements.

BACKGROUND: Gastroesophageal reflux disease (GERD) in patients with neurological impairment (NI) has not been fully studied before and after fundoplication procedure because their characteristics such as generalized gastrointestinal dysmotility, non-acid reflux, and the proximal reflux due to feeding of enteral nutrition via a nasogastric tube prevent their GERD from being detected by 24 h pH monitoring. The aim of this study was to elucidate whether multichannel impedance-pH measurement (pH/MII) is able to detect the subtypes of GERD and the differences in the reflux episodes of the severity of GERD, the ingestion pathway, and before and after fundoplication. The second aim was to determine whether a trial evaluation of dry swallows was able to be used to assess the esophageal motility of NI patients as an alternative examination. PATIENTS AND METHODS: The 24 h pH/MII was conducted on 20 NI children [15 were the patients before Nissen's fundoplication (BN), of whom, six were fed orally (FO) and nine were fed via nasogastric tube (NGT), and five were the patients after Nissen's fundoplication (AN)]. All reflux episodes were evaluated and compared between patients with pathological GERD (PG) and non-pathological GERD (NG) and between patients who had FO and NGT and patients between BN and AN. Dry swallows were conducted to evaluate the esophageal motility. The average bolus presence time (BPT) and total bolus transit time (TBTT) were compared between the PG and NG, FO and NGT, and the BN and AN subgroups. RESULTS: A total of 1,064 reflux episodes were detected by pH/MII. Of those, 303 (28.5 %) were non-acid-related and 477 episodes reached the proximal esophagus. Of the 12 patients (57.1 %) showing pathological GERD, two cases (16.7 %) demonstrated predominantly weakly acidic PG. More than half of the reflux episodes of PG patients reached to the proximal esophagus. The numbers of total reflux and proximal reflux episodes in the PG were significantly higher than those in NG patients. The number of proximal reflux episodes in the FO group was significantly higher than that in the NGT groups, whereas NGT patients showed more non-acidic reflux episodes than FO patients. A trial evaluation of dry swallows demonstrated no significant differences in this study. CONCLUSION: The pH/MII was useful to detect the subtype of GERD in NI patients which could not be detected by 24 h pH monitoring. It can, therefore, be considered to have first priority for testing NI patients who are suspected to be suffering from GERD.

Infantile neuroblastoma of the urinary bladder detected by hematuria.

Malignant tumors of the urinary bladder in infants are extremely rare. Rhabdomyosarcoma is the most likely tumor in this site, whereas neuroblastoma of the urinary bladder is exceedingly uncommon and is not listed as a differential diagnosis for tumors of this site. We present a case of neuroblastoma arising from the dome of the bladder wall, detected by hematuria. Only six cases of neuroblastoma originating from the bladder, including the present case have been reported. Of the cases, five arose from the dome of the bladder wall. In this report, the differential diagnosis of bladder tumors in children is discussed. A diagnosis of neuroblastoma should be taken into consideration, especially in the case of tumors arising from the dome of the bladder wall despite an uncommon location.